Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92093, USA.
J Leukoc Biol. 2010 Oct;88(4):737-45. doi: 10.1189/jlb.0310131. Epub 2010 Jul 19.
Coronin-1A is a WD repeat protein family member, highly expressed in all hematopoietic lineages, and acts as a regulator of F-actin dynamics and Ca2+ signaling. In Coro1a(Lmb3) mice results in inactivation of the protein and leads to disease resistance in a model of lupus erythematosus. In Coro1a(-/-) and Coro1a(Lmb3) mice, peripheral T cells exhibit impairments in survival, migration, activation, and Ca2+ flux. In this study, we show that in vitro-differentiated mast cells from Coro1a(Lmb3) mice are viable, developed normally, and are fully functional in assays of degranulation, cytokine secretion, and chemotactic migration, despite increased F-actin levels. In Coro1a(Lmb3) mast cells, Ca2+ flux in response to physiological FcεRI stimulation is unaffected. Finally, Coro1a(Lmb3) mice showed similar in vivo mast cell responses as the WT mice. Coronin-1B and Coronin-1C expression levels were not increased in Coro1a(Lmb3) mast cells but were higher in mast cells than in CD4 T cells or B cells in WT mice. We conclude that Coronin-1A activity is not required for mast cell function.
冠状蛋白-1A 是 WD 重复蛋白家族的一员,在所有造血谱系中高度表达,作为 F-肌动蛋白动力学和 Ca2+信号的调节剂。在 Coro1a(Lmb3)小鼠中,该蛋白失活导致红斑狼疮模型中疾病抵抗力增强。在 Coro1a(-/-)和 Coro1a(Lmb3)小鼠中,外周 T 细胞在存活、迁移、激活和 Ca2+流方面存在缺陷。在这项研究中,我们表明,来自 Coro1a(Lmb3)小鼠的体外分化肥大细胞是存活的、正常发育的,并在脱颗粒、细胞因子分泌和趋化性迁移测定中具有完全功能,尽管 F-肌动蛋白水平增加。在 Coro1a(Lmb3)肥大细胞中,对生理 FcεRI 刺激的 Ca2+流不受影响。最后,Coro1a(Lmb3)小鼠显示出与 WT 小鼠相似的体内肥大细胞反应。Coro1a(Lmb3)肥大细胞中的 Coronin-1B 和 Coronin-1C 表达水平没有增加,但在 WT 小鼠中高于 CD4 T 细胞或 B 细胞。我们得出结论,冠状蛋白-1A 的活性不是肥大细胞功能所必需的。